The objective of this study is to investigate the mechanism of neoplastic cell escape from host immune defense system. Since the Fc receptor on the immune effector cells has been reported to be the physical site of interaction between the tumor target cells and effector cells in the antibody-dependent cellular cytotoxicity, then any Fc receptor being released into the system could inhibit this important immune effector function. We have observed that L5178Y lymphoma were shedding Fc receptor into the ascitic fluid in a function of tumor growth. The release of Fc receptor into ascitic fluid by tumor cells or other cells could have great possibility of protecting any tumor cells carrying antibodies to escape the immune effector function of ADCC. In an effort to study the biochemical mechanisms involved in ADCC reaction, we have observed three protease inhibitors, namely, tosyl-L-phenylalanine, tosyl-L-alanine and 1, 10-phenylanthroline, were able to suppress the ADCC activity of rat spleen cells. The effect of these three protease inhibitors on the ADCC inhibition did not take place at the initial phase of binding effector cell Fc receptor to the antibody on target cell because these inhibitors failed to have any effect on the effector cell's ability to form EoxA rosettes. Thus, this observation supports the thesis that the Fc receptor binding itself is not sufficient to cause lysis of target cells.